How does p53 contribute to apoptosis?

The p53 protein is a tumour suppressor gene product that helps maintain the health of a cell. It does this by sensing DNA damage or other cell stress. When the damage inside the cell is too much and cannot be repaired, p53 contributes to the process of apoptosis, which means programmed cell death. This way, it helps remove damaged cells so they do not become cancerous.

How p53 Contributes to Apoptosis

It mainly works in three ways:

1. It Increases the Production of Pro-apoptotic Proteins

When p53 is activated, it goes into the nucleus and starts the production (transcription) of special genes that promote cell death. These include:
  • BAX: It helps in making holes in the mitochondrial membrane, which is an important step in cell death.
  • PUMA and NOXA: These are small proteins that support BAX and stop the proteins that try to save the cell.
All these proteins act together and start the mitochondrial (intrinsic) pathway of apoptosis.

2. It Helps Release Cytochrome c from Mitochondria

Because of BAX and PUMA, the outer membrane of mitochondria becomes leaky. From there, a protein called cytochrome c comes out. This cytochrome c joins with Apaf-1 and forms a structure called the apoptosome.

This structure activates caspase enzymes (like caspase-9 and caspase-3), which are responsible for breaking down the cell slowly and safely.

3. It Blocks the Proteins That Prevent Apoptosis

p53 also stops the proteins that normally try to save the cell, such as:
  • Bcl-2
  • Survivin
By blocking them, p53 makes sure that the cell moves forward towards apoptosis if the damage is too much.







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